Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists最新文献

The role of transforming growth factor-beta (TGF-beta) in epithelial malignancy is complex, but it is becoming clear that, in the early stages of carcinogenesis, the protein acts as a potent tumor suppressor, while later, TGF-beta can function to advance tumor progression. We review the evidence to show that the pro-oncogenic functions of TGF-beta are associated with (1) a partial loss of response to the ligand, (2) defects of components of the TGF-beta signal transduction pathway, (3) over-expression and/or activation of the latent complex, (4) epithelial-mesenchymal transition, and (5) recruitment of signaling pathways which act in concert with TGF-beta to facilitate the metastatic phenotype. These changes are viewed in the context of what is known about the pathogenesis of oral cancer and whether this knowledge can be translated into the development of new therapeutic modalities.

During the last two decades, there has been an increasing interest in the impact of oral health on atherosclerosis and subsequent cardiovascular disease (CVD). The advent of the inflammation paradigm in coronary pathogenesis stimulated research in chronic infections caused by a variety of micro-organisms-such as Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus-as well as dental pathogens, since these chronic infections are thought to be involved in the etiopathogenesis of CVD by releasing cytokines and other pro-inflammatory mediators (e.g., C-reactive protein [CRP], tumor necrosis factor [TNF-alpha]) that may initiate a cascade of biochemical reactions and cause endothelial damage and facilitate cholesterol plaque attachment. Yet, due to the multi-factorial nature of dental infection and CVD, confirming a causal association is difficult, and the published results are conflicting. The main deficit in the majority of these studies has been the inadequate control of numerous confounding factors, leading to an overestimation and the imprecise measurement of the predictor or overadjustment of the confounding variables, resulting in underestimation of the risks. A meta-analysis of prospective and retrospective follow-up studies has shown that periodontal disease may increase the risk of CVD by approximately 20% (95% confidence interval [CI], 1.08-1.32). Similarly, the reported risk ratio between periodontal disease and stroke is even stronger, varying from 2.85 (CI 1.78-4.56) to 1.74 (CI 1.08-2.81). The association between peripheral vascular disease and oral health parameters has been explored in only two studies, and the resultant relative risks among individuals with periodontitis were 1.41 (CI 1.12-1.77) and 2.27 (CI 1.32-3.90), respectively. Overall, it appears that periodontal disease may indeed contribute to the pathogenesis of cardiovascular disease, although the statistical effect size is small.

The transforming growth factor-beta (TGF-beta) family of cytokines consists of multi-functional polypeptides that regulate a variety of cell processes, including proliferation, differentiation, apoptosis, extracellular matrix elaboration, angiogenesis, and immune suppression, among others. In so doing, TGF-beta plays a key role in the control of cell behavior in both health and disease. In this report, we review what is known about the mechanisms of activation of the peptide, together with details of TGF-beta signal transduction pathways. This review summarizes the evidence implicating TGF-beta in normal physiological processes of the craniofacial complex-such as palatogenesis, tooth formation, wound healing, and scarring-and then evaluates its role in non-malignant disease processes such as scleroderma, submucous fibrosis, periodontal disease, and lichen planus.

Apical periodontitis is a sequel to endodontic infection and manifests itself as the host defense response to microbial challenge emanating from the root canal system. It is viewed as a dynamic encounter between microbial factors and host defenses at the interface between infected radicular pulp and periodontal ligament that results in local inflammation, resorption of hard tissues, destruction of other periapical tissues, and eventual formation of various histopathological categories of apical periodontitis, commonly referred to as periapical lesions. The treatment of apical periodontitis, as a disease of root canal infection, consists of eradicating microbes or substantially reducing the microbial load from the root canal and preventing re-infection by orthograde root filling. The treatment has a remarkably high degree of success. Nevertheless, endodontic treatment can fail. Most failures occur when treatment procedures, mostly of a technical nature, have not reached a satisfactory standard for the control and elimination of infection. Even when the highest standards and the most careful procedures are followed, failures still occur. This is because there are root canal regions that cannot be cleaned and obturated with existing equipments, materials, and techniques, and thus, infection can persist. In very rare cases, there are also factors located within the inflamed periapical tissue that can interfere with post-treatment healing of the lesion. The data on the biological causes of endodontic failures are recent and scattered in various journals. This communication is meant to provide a comprehensive overview of the etio-pathogenesis of apical periodontitis and the causes of failed endodontic treatments that can be visualized in radiographs as asymptomatic post-treatment periapical radiolucencies.

Background: Periodontal disease results in the loss of the attachment apparatus. In the last three decades, an increasing effort has been placed on seeking procedures and materials to promote the regeneration of this tissue. The aim of this paper is to evaluate the effect of enamel matrix derivative (EMD) during regenerative procedures. In addition, a meta-analysis is presented regarding the clinical results during regeneration with EMD, to gain evidence as to what can be accomplished following treatment of intrabony defects with EMD in terms of probing depth reduction, clinical attachment level gain, defect fill (using re-entry studies), and radiographic parameters.

Methods: The review includes in vitro and in vivo studies as well as human case reports, clinical comparative trials, and histologic findings. In addition, a meta-analysis is presented regarding the regenerative clinical results. For this purpose, we used 28 studies-including 955 intrabony defects treated with EMD that presented baseline and final data on probing depth, clinical attachment level (CAL) gain, or bone gain-to calculate weighted mean changes in the different parameters. The selected studies were pooled from the MEDLINE database at the end of May, 2003.

Results: The meta-analysis of intrabony defects treated with EMD resulted in a mean initial probing depth of 7.94 +/- 0.05 mm that was reduced to 3.63 +/- 0.04 mm (p = 0.000). The mean clinical attachment level changed from 9.4 +/- 0.06 mm to 5.82 +/- 0.07 mm (p = 0.000). These results were significantly better than the results obtained for either open-flap debridement (OFD) or guided tissue regeneration (GTR). In contrast, histologically, GTR is more predictable than EMD in terms of bone and cementum formation. No advantage was found for combining EMD and GTR. Xenograft, or EMD and xenograft, yielded inferior results compared with EMD alone, but a limited number of studies evaluated this issue. Promising results were noted for the combination of allograft materials and EMD.

Conclusions: EMD seems to be safe, was able to regenerate lost periodontal tissues in previously diseased sites based on clinical parameters, and was better than OFD or GTR. Its combination with allograft materials may be of additional benefit but still needs to be further investigated.

Cellular and molecular processes that regulate the development of skeletal tissues resemble those required for regeneration. Given the prevalence of degenerative skeletal disorders in an increasingly aging population, the molecular mechanisms of skeletal development must be understood in detail if novel strategies are to be developed in regenerative medicine. Research in this area over the past decade has revealed that cell differentiation is largely controlled at the level of gene transcription, which in turn is regulated by transcription factors. Transcription factors usually recognize and bind to specific DNA sequences in the promoter of target genes via characteristic DNA-binding domains. Although the gene family containing C2H2 zinc fingers as DNA-binding motifs is the largest family of transciptional regulators, with several hundred individual members in mammals, only a small but increasing number of zinc finger genes have been implicated in bone, cartilage, or tooth development. These zinc finger proteins (ZFPs) contain multiple structural motifs that require zinc to maintain their structural integrity and function. Interestingly, zinc deficiency is known to result in skeletal growth retardation and has been identified as a risk factor in the pathogenesis of osteoporosis. This review attempts to summarize our current state of knowledge regarding the role of ZFPs in the molecular regulation of skeletogenesis.

Recent efforts on developing more direct and effective targets for cancer therapy have revolved around a family of transcription factors known as STATs (signal transducers and activators of transcription). STAT proteins are latent cytoplasmic transcription factors that become activated in response to extracellular signaling proteins. STAT proteins have been convincingly reported to possess oncogenic properties in a plethora of human cancers, including oral and oropharyngeal cancer. Signal transduction pathways mediated by these oncogenic transcription factors and their regulation in oral cancer are the focus of this review.

Enterococcus faecalis is a micro-organism that can survive extreme challenges. Its pathogenicity ranges from life-threatening diseases in compromised individuals to less severe conditions, such as infection of obturated root canals with chronic apical periodontitis. In the latter situation, the infecting organisms are partly shielded from the defense mechanisms of the body. In this article, we review the virulence factors of E. faecalis that may be related to endodontic infection and the periradicular inflammatory response. The most-cited virulence factors are aggregation substance, surface adhesins, sex pheromones, lipoteichoic acid, extracellular superoxide production, the lytic enzymes gelatinase and hyaluronidase, and the toxin cytolysin. Each of them may be associated with various stages of an endodontic infection as well as with periapical inflammation. While some products of the bacterium may be directly linked to damage of the periradicular tissues, a large part of the tissue damage is probably mediated by the host response to the bacterium and its products.

The last 350 years since the publication of the first medical monograph on rickets (old English term wrickken) (Glisson et al., 1651) have seen spectacular advances in our understanding of mineral-homeostasis. Seminal and exciting discoveries have revealed the roles of PTH, vitamin D, and calcitonin in regulating calcium and phosphate, and maintaining healthy teeth and skeleton. However, it is clear that the PTH/Vitamin D axis does not account for the entire picture, and a new bone-renal metabolic milieu has emerged, implicating a novel set of matrix proteins, hormones, and Zn-metallopeptidases. The primary defects in X-linked hypophosphatemic rickets (HYP) and autosomal-dominant hypophosphatemic rickets (ADHR) are now identified as inactivating mutations in a Zn-metalloendopeptidase (PHEX) and activating mutations in fibroblast-growth-factor-23 (FGF23), respectively. In oncogenic hypophosphatemic osteomalacia (OHO), several tumor-expressed proteins (MEPE, FGF23, and FRP-4) have emerged as candidate mediators of the bone-renal pathophysiology. This has stimulated the proposal of a global model that takes into account the remarkable similarities between the inherited diseases (HYP and ADHR) and the tumor-acquired disease OHO. In HYP, loss of PHEX function is proposed to result in an increase in uncleaved full-length FGF23 and/or inappropriate processing of MEPE. In ADHR, a mutation in FGF23 results in resistance to proteolysis by PHEX or other proteases and an increase in half-life of full-length phosphaturic FGF23. In OHO, over-expression of FGF23 and/or MEPE is proposed to result in abnormal renal-phosphate handling and mineralization. Although this model is attractive, many questions remain unanswered, suggesting a more complex picture. The following review will present a global hypothesis that attempts to explain the experimental and clinical observations in HYP, ADHR, and OHO, plus diverse mouse models that include the MEPE null mutant, HYP-PHEX transgenic mouse, and MEPE-PHEX double-null-mutant.